The overall aim is to explore the control of myelination in the mammalian nervous system. The specific objective is to study in the peripheral nervous system of the rat, the role of the axon in the control of myelination. The first goal is to determine if the axon instructs the myelinating cell to commence myelination. Here we will employ our proven model of cross-anastomosis between myelinated and unmyelinated nerves to examine, using a H3-thymidine tracer, the origin of Schwann cells which form myelin normally in the distal stump of the unmyelinated nerve around axons which have regenerated from the proximal stump of the foreign, myelinated nerve. Second, the putative axonal factor which triggers Schwann cell myelinogenesis will be sought using radioactive macromolecular precursors, introduced into the lower lumbar spinal cord, incorporated into anterior horn neurons and transported down the peroneal nerve to a position of focal demyelination and remyelination which will be produced by creating a perineurial window. The time of arrival of the peak of fast transported label will first be determined by liquid scintillation spectrometry in the normal nerve. Our foucs will then shift to nerves with perineurial windows where the presence of residual label in the lesion will be studied at stages of demyelination and remyelination, after the fast peak has traveled past the lesion. Ultrastructurally-fixed single teased nerve fibers will be prepared for autoradiography and the distribution of the label in the axon and Schwann cells studied by Nomarski differential interference microscopy. Tracers to be employed include tritiated and carbon-14 amino acids to label transported peptides and proteins, H3 uridine to label RNA, H3 fucose to label glycoprotein, and tritiated cyclic AMP. After establishing which materials leak from the axon to the Schwann cell at the site of demyelination, we will block transport of the material using proximal nerve cuffs containing lidocaine and attempt thereby to delay or retard remyelination. Results of these experiments will bear heavily on our understanding of the interrelationship between the neuron, its axon and the myelinating cell, and factors which control myelinogenesis. Such data might provide some direction for the amelioration of human nervous system diseases which are characterized by abnormalities of myelin.